Regulation of Stationary Phase in Escherichia coli

描述(申请人提供)：肠道细菌，如大肠杆菌，一生中的大部分时间都在饥饿中寻找一种或多种必需的营养物质。为了在饥饿条件下的环境挑战中生存下来，这些细菌进入了一种被称为静止期的不生长状态。固定相的主调节器是交替的主西格玛因子rpos。在快速生长的细胞中，rpos水平很低，因为孤儿反应调节因子SprE(RSSB)的目标是Rpos被CIPP/X蛋白酶降解。我们发现，当细菌缺乏碳时，RPOS水平会增加，因为RPOS的降解停止了。磷饥饿也会导致rpos水平升高，但在这种情况下，由于rpos mRNA翻译增加，rpos水平升高。相反，氮素饥饿并不会导致RPOS水平的增加；相反，RPOS的活性会增加。我们提出了一种结合遗传、生化、代谢和计算的方法来确定关键的信号和效应分子，这些分子介导了对营养缺乏的这些不同的反应。由于RPOS已知在某些细菌的发病机制中起重要作用，详细了解细菌如何进入和离开稳定期可能会揭示这些病原体盔甲中的裂缝。此外，由于中枢新陈代谢途径在整个生物学中都是保守的，我们认为触发向非生长状态转变的信号也可能是保守的。因此，在细菌中获得的洞察力可能有助于揭示真核微生物的类似过程，或许动物细胞也是如此。

DESCRIPTION (provided by applicant): Enteric bacteria such as Escherichia coli spend most of their lifetimes starved for one or more essential nutrients. To survive environmental challenges under starvation conditions these bacteria enter a non-growing state called stationary phase. The master regulator of stationary phase is the alternate primary sigma factor RpoS. In rapidly growing cells RpoS levels are low because the orphan response regulator SprE (RssB) targets RpoS for degradation by the CIpP/X protease. We have discovered that when bacteria are starved for carbon, RpoS levels increase because RpoS degradation stops. Starvation for phosphorus also results in elevated levels of RpoS, but in this case levels are elevated because of an increase in rpoS mRNA translation. In contrast starvation for nitrogen does not cause an increase in RpoS levels; rather, RpoS activity is increased. We propose a combination of genetic, biochemical, metabolomic, and computational methods to identify the key signaling and effector molecules that mediate these diverse responses to nutrient deprivation. Since RpoS is known to be important for the pathogenesis of certain bacteria, a detailed understanding of how bacteria enter and exit stationary phase may reveal chinks in the armor of these pathogens. In addition, because the pathways of central metabolism are conserved throughout biology, we think that the signals that trigger transition to a non-growing state may be conserved as well. Thus insights gained in bacteria may shed light on similar processes in eukaryotic microbes, and perhaps animal cells as well.